Author:
Bullen Alexander L.,Katz Ronit,Poursadrolah Sayna,Short Samuel A. P.,Long D. Leann,Cheung Katharine L.,Sharma Shilpa,Al-Rousan Tala,Fregoso Alma,Schulte Janin,Gutierrez Orlando M.,Shlipak Michael G.,Cushman Mary,Ix Joachim H.,Rifkin Dena E.
Abstract
Abstract
Background
Plasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.S.
Methods
In a nested cohort of 4,400 participants among the REasons for Geographic And Racial Differences in Stroke, we determined the association between baseline PENK-A concentration and incident CKD using the creatinine-cystatin C CKD-EPI 2021 equation without race coefficient, significant eGFR decline, and incident albuminuria between baseline and a follow-up visit 9.4 years later. We tested for race and sex interactions. We used inverse probability sampling weights to account for the sampling design.
Results
At baseline, mean (SD) age was 64 (8) years, 49% were women, and 52% were Black participants. 8.5% developed CKD, 21% experienced ≥ 30% decline in eGFR and 18% developed albuminuria. There was no association between PENK-A and incident CKD and no difference by race or sex. However, higher PENK-A was associated with increased odds of progressive eGFR decline (OR: 1.12; 95% CI 1.00, 1.25). Higher PENK-A concentration was strongly associated with incident albuminuria among patients without diabetes mellitus (OR:
1.29; 95% CI 1.09, 1.53).
Conclusion
While PENK-A was not associated with incident CKD, its associations with progression of CKD and incident albuminuria, among patients without diabetes, suggest that it might be a useful tool in the evaluation of kidney disease among White and Black patients.
Funder
U.S. Department of Veterans Affairs
National Institute of Diabetes and Digestive and Kidney Diseases
Publisher
Springer Science and Business Media LLC
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